The aim of this study was to explore the mechanism resulting in hypoventilation in rats with denervated diaphragm. Bilateral cervical phrenicotomy (PX) was performed in 15 male rats anaesthetized with urethane (1.3 g/kg i p ); other 8 rats were sham operated (SX). Ventilation, PaCo2 and the integrated EMG of the external intercostal muscles (iEMG) were measured before and after the surgery, at regular intervals, up to 4 hours postoperatively. During the 4 hours after PX there was a progressive decrease in minute ventilation and an increase in Paco2 compared with the control values and with that in the SX rats. The increase in PaC02 was accompanied by an increase in the peak amplitude of the ifiMG to 155±18 % of control values after PX and to 228±33 9\ 4 hours later. Despite the augmented IMG activity tidal volume gradually decreased. The iEMG of the intercostal muscles, however, did not reach a maximum because the shortlasting stimulation of breathing by acute hypercapnia and hypoxia as the result of added dead space (0.5 ml) increased the iEMG still further. These results indicate that both the central and peripheral mechanisms contribute to hypoventilation in anaesthetized rats with denervated diaphragm.